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Purpose: This study sought to explore the effect of intraoperative mean blood glucose levels and variability on postoperative acute kidney injury (AKI) in children undergoing congenital cardiac surgery. Methods: We conducted a prospective nested case-control study in children (age< 18 years) undergoing congenital heart surgery with cardiopulmonary bypass (CPB) at the Fuwai Hospital between April 01, 2022 and July 30, 2022. Cases were individuals who developed AKI within the first postoperative 7 days (AKI group) and controls were those without AKI (Non-AKI group) according to KDIGO criteria. AKI and Non-AKI groups unmatched and 1:1 matched by age, sex, and baseline serum creatinine were separately analyzed. Multivariate logistic and conditional logistic regressions were used to assess the associations between blood glucose variables and AKI. Results: 688 consecutively approached patients were included in the final analysis. On multivariate analysis, intra-CPB (adjusted odds ratio [OR] 0.802; 95% confidence interval [CI], 0.706 to 0.912; p = 0.001) and post-CPB (adjusted OR 0.830; 95% CI, 0.744 to 0.925; p = 0.001) blood glucose levels were associated with postoperative AKI. There were no significant differences in pre-CPB blood glucose (adjusted OR 0.926; 95% CI, 0.759 to 1.129; p = 0.446) or intraoperative glycemic fluctuations (adjusted OR 0.905; 95% CI, 0.723 to 1.132; p = 0.382) between AKI and Non-AKI groups. Results based on matched cases and controls were consistent with those from the unmatched analyses. Conclusion: Higher intraoperative blood glucose levels during and after CPB were protective factors against post- operative AKI in pediatric patients after congenital heart surgery. [ABSTRACT FROM AUTHOR]